Abstract
Few studies have been undertaken to assess the possible effects of bisphenol A (BPA) on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5–17.5 days post-coitum) and humans (8–12 gestational weeks) and under different culture conditions. BPA concentrations of 10-8M and 10-5M for 72h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48h in both strains. BPA at 10-7-10-5M for 72h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3). BPA exposure at 10-8M, 10-7M, and 10-5M for 72h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i) BPA can display anti-androgenic effects both in rat and human fetal testes; (ii) it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii) the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv) due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA.
Highlights
Of the thousands of anthropogenic chemicals present in the environment, those suspected of posing a threat to the health of the living organisms by disrupting their endocrine systems, referred to as endocrine-disrupting chemicals (EDCs), have attracted much attention over the past two decades
In utero exposure of Sprague-Dawley rats to 40 mg/kg/day [20] or 500 mg/kg/day bisphenol A (BPA) [21] was not associated with any change in the anogenital distance (AGD), which reflects in utero exposure to androgens in male pups
This finding indicates that no biotransformation of BPA took place
Summary
Of the thousands of anthropogenic chemicals present in the environment, those suspected of posing a threat to the health of the living organisms by disrupting their endocrine systems, referred to as endocrine-disrupting chemicals (EDCs), have attracted much attention over the past two decades. Other EDCs have drawn attention due to their potential effects in mammals on the development and functions of reproductive organs, which depends crucially on hormones These include phthalates, which are widely used, in the plastics and pesticide industries, among others (recently reviewed by Albert & Jégou 2014 [12]). Only a few studies have so far examined this issue for BPA by either toxicological or epidemiological assessments (recently reviewed by Rochester 2013 [13]) They have shown that BPA doses below the current reference exposure limits for humans can impair reproductive physiology in CF-1 mice ([14]; 2.4 μg/kg) and induce nonsocial behavior in Sprague-Dawley rats ([15]; 40 μg/kg/day). Exposure of pregnant Wistar-Furth rats to 250 μg/kg/day did reduce the AGD in their male pups and reflected a deficiency in androgen production or action [22]
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